Numerous proteins and peptides, collectively referred to herein as polypeptides, exhibit biological activity in vivo, which renders them useful as medicaments in therapy. Many illnesses or conditions which can be treated with a biologically active polypeptide, require administration of a constant or sustained level of medicament to provide the most effective prophylactic and/or therapeutic effects. As such, administration of biologically active polypeptides can require frequent subcutaneous injections, which result in fluctuating levels of medicament and poor patient compliance.
As an alternative, the use of biodegradable materials, such as polymers, encapsulating the medicament can be employed as a sustained delivery system. The use of biodegradable polymers, for example, in the form of microparticles or microcarriers, can provide a sustained release of medicament, by utilizing the inherent biodegradability of the polymer to control the release of the medicament thereby providing a more consistent, sustained level of medicament and improved patient compliance.
However, these sustained release devices can exhibit high initial bursts of medicament and minimal release thereafter, resulting in serum drug levels outside the therapeutic window and/or poor bioavailability of the medicament. In addition, the presence of polymer, physiological temperatures and body response to the sustained release composition can cause the medicament to be altered (e.g., degraded, aggregated) thereby interfering with the desired release profile for the medicament.
Further, methods used to form sustained release compositions can result in loss of activity of the medicament due to the instability of the medicament and the degradative effects of the processing steps. Degradative effects are particularly problematic when the medicament is a polypeptide.
Therefore, a need exists for a means of administering biologically active polypeptides in a sustained fashion wherein the amount of polypeptide delivered is at therapeutic levels, and retains activity and potency for the desired period of release.